DESCRIPTION: The applicant plans to synthesize and spectroscopically characterize novel symmetric organorhenium(I) and organotechnetium(I) lipophilic cationic complexes targeted to the MDR1 P-glycoprotein, specifically exploring the effects of: a) combining aromatic ring halogenation with ether functionalities, and b) alkyl spacers positioned between the substituted aryl and isonitrilic moieties; to explore an alternative chemical pathway for synthesis of a closely related class of novel mixed ligand rhenium(III) isonitrile-metal complexes to enhance the chances for success in producing bioactive Re-complexes; use his MDR bioassays to screen and characterize novel metal-isonitrile complexes for modulation of P-glycoprotein transport function; and, to perform preclinical validation of in vivo of promising lead metal-isonitrile modulators.